1. Field of the Invention
The discovery that one could introduce exogenous genes into a bacterial host in vitro and observe expression of the exogenous genes in the bacterial host opened up vistas of new capabilities for the production of a wide range of compounds, particularly proteins, improved methods of treating waste, novel types of fertilizers, and new vaccines. While transformation of prokaryotes offer many new and yet envisaged opportunities, there is also great interest in being able to modify eukaryotes and particularly mammalian cells.
Many diseases are genetically related involving genetic deficiencies, which are usually either failure to produce a gene product or production of an abnormal product. Other situations involve treatment of a host with drugs which may have substantial toxicity to host cells. In these instances, it would be desirable to provide the host with the missing capability, the normal capability or a defense mechanism against the detrimental effects of the drug. The capability to modify a host's genetic structure to provide for either additional genetic capabilities or reparation of a defective capability on a temporary or permanent basis opens up wide avenues in the treatment of genetic deficiencies and disease.
2. Description of the Prior Art
Methods of introducing genetic material into a host cell include viral vectors Munyon et al. J. Virol, 7:813-820, 1971; cell-cell fusion, the fusion to cells of a limited number of chromosomes enveloped in nuclear membranes, Fournier et al. Proc. Natl. Acad. Sci. 74:319-323, 1977; and cellular endocytosis of microprecipitates of calcium-DNA complex, Bachetti and Graham, ibid. 74:1590-1594, 1977; Maitland and McDougall, Cell 11:233-241, 1977; Pellicer et al. ibid. 14:133-141, 1978 and Wigler et al. ibid. 14:725-731, 1978. Cell lines lacking thymidine kinase are readily transformed by appropriate DNA to a tk.sup.+ status when grown in the presence of a folic acid inhibitor and thymidine. Pellicer, supra and Wigler, supra.